Case Report: A child with NFKB1 haploinsufficiency explaining the linkage between immunodeficiency and short stature

Front Immunol. 2023 Aug 3:14:1224603. doi: 10.3389/fimmu.2023.1224603. eCollection 2023.

Abstract

We report the case of a patient with common variable immunodeficiency (CVID) presenting with short stature and treated with recombinant human growth hormone (rhGH). Whole exome sequencing revealed a novel single-nucleotide duplication in the NFKB1 gene (c.904dup, p.Ser302fs), leading to a frameshift and thus causing NFKB1 haploinsufficiency. The variant was considered pathogenic and was later found in the patient's mother, also affected by CVID. This is the first reported case of a patient with CVID due to NFKB1 mutation presenting with short stature. We analyzed the interconnection between NFKB1 and GH - IGF-1 pathways and we hypothesized a common ground for both CVID and short stature in our patient.

Keywords: NFKB1; common variable immunodeficiency; growth hormone; short stature; whole exome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Common Variable Immunodeficiency* / diagnosis
  • Common Variable Immunodeficiency* / genetics
  • Female
  • Frameshift Mutation
  • Haploinsufficiency
  • Humans
  • Immunologic Deficiency Syndromes*
  • Mothers
  • NF-kappa B p50 Subunit / genetics

Substances

  • NFKB1 protein, human
  • NF-kappa B p50 Subunit

Grants and funding

The study was supported by the CVIDOME project (Tuscany Health Research Grant 2018).